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image of Stem Cells Derived From Human Deciduous Exfoliated Teeth Ameliorate Adriamycin-Induced Nephropathy In Rats By Modulating The Th17/Treg Balance

Abstract

Background

Idiopathic Nephrotic Syndrome (INS) is a common kidney disease in children, and the main clinical manifestations are hypoproteinaemia, proteinuria, hyperlipidaemia, and oedema. Mesenchymal Stem Cells (MSCs) are involved in tissue repair, protection against fibrosis, and immune modulation but have rarely been studied in INS.

Objective

This study aimed to explore the therapeutic potential of stem cells derived from human exfoliated deciduous teeth (SHEDs) in INS using an adriamycin-induced nephropathy (AN) rat model.

Methods

AN was induced in Sprague‒Dawley rats, and SHEDs were transplanted the tail vein in single (SHED-s) and multidose (SHED-m) regimens. Cell migration assays were used to track the SHED distribution. Weight, urine protein, and serum biochemical assays were also performed. HE and Masson staining were used to observe glomerular and tubular damage, as well as the degree of fibrosis. Immunohistochemistry was used to label T lymphocytes and podocytes, and structural changes in podocytes were observed by electron microscopy. ELISA was used to measure the levels of inflammatory factors. Flow cytometry was used to analyse the balance of Th17 cells and Tregs. The mRNA expression of Th17- and Treg-associated cytokines and specific transcription factors was examined by RT‒PCR.

Results

SHEDs directly migrated to damaged tissues, suggesting a targeted therapeutic effect. SHED transplantation significantly reduced proteinuria and reversed biochemical abnormalities in rats with AN. Both single and multidose SHED treatments could inhibit glomerular and tubular damage and delay the progression of fibrosis caused by adriamycin. SHEDs exerted a protective effect on podocytes. Additionally, this treatment inhibited inflammatory responses and corrected immune imbalances, as evidenced by decreased T lymphocyte infiltration, reduced serum levels of IL-6, TNF-a, and IL-1β, and modulation of the Th17/Treg balance.

Conclusion

In the AN rat model, SHED partly suppressed the development of inflammation and alleviated kidney injury, and immune regulation may be the underlying mechanism.

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2024-12-20
2025-01-22

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/content/journals/cscr/10.2174/011574888X336035241209065513
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Stem Cells Derived From Human Deciduous Exfoliated Teeth Ameliorate Adriamycin-Induced Nephropathy In Rats By Modulating The Th17/Treg Balance
Bentham Science Publishers ; https://doi.org/10.2174/011574888X336035241209065513
/content/journals/cscr/10.2174/011574888X336035241209065513
/content/journals/cscr/10.2174/011574888X336035241209065513
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  • Article Type:     Research Article
Keywords: podocyte ; Idiopathic nephrotic syndrome ; adriamycin-induced nephropathy ; stem cells derived from human deciduous exfoliated teeth

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